Adhesions are unwanted tissue growths occurring between layers of adjacent bodily tissue or between tissues and internal organs. Adhesions are often formed during the dynamic process of healing of the incision and tissue trauma after surgery. The initiation of the adhesion begins with the formation of a fibrin matrix. The ischemic conditions caused by surgery prevent fibrinolytic activity to dissolve the matrix, and the fibrin persists. Wound repair cells then turn the matrix into an organized adhesion, often having a vascular supply and neuronal elements. Adhesions can prevent the normal motions of tissues and organs with respect to their neighbouring structures. Adhesions are a particular problem in gastrointestinal and gynecological surgery, leading to post-operative bowel obstruction, infertility, and chronic pelvic pain.
The medical and scientific communities have studied ways of reducing the formation of post-surgical adhesions by the use of high molecular weight carboxyl-containing biopolymers. These biopolymers can form hydrated gels which act as physical barriers to separate tissues from each other during healing, so that adhesions between normally adjacent structures do not form. After healing is substantially complete, the barrier is no longer needed, and should be eliminated from the body to permit more normal function of the affected tissues.
KR 2001 107 067 describes an adhesion preventing agent comprising 1.0-15 wt % of alginate having a viscosity of 150 centipoise, 0-2.5 wt % of polyethylene glycol having a molecular weight of 3,000-5,000, 0-8 wt % of agarose, 0-1 wt. % of an antibiotic, and 73.5-99.0 wt % of water. The adhesion preventing agent is sterilized at a temperature of less than 150° C. for 5-20 minutes.
U.S. Pat. No. 6,150,581 (United States Surgical Corporation) describes a method for preventing post surgical adhesions comprising:                providing an aqueous solution of chitosan and a complexing agent;        providing an aqueous solution of alginate; and        combining the chitosan/complexing agent solution with the alginate solution to form an anti-adhesion barrier at a site of surgical intervention.        
U.S. Pat. No. 6,638,917 (Boston Scientific SciMed, Inc) describe a method of forming a sheet for use as an adhesion barrier, comprising:                forming a film from an alginate solution; and        contacting the film with a cross-linking solution to form a cross-linked mechanically stable sheet for placement of at least a portion of the sheet at a site of trauma to create the adhesion barrier        
WO 2006/044342 A2 (FMC Biopolymer AS) describes a method of using a self gelling alginate dispersion to prevent post surgical adhesion formation in an individual, said method comprising dispensing a self gelling alginate dispersion within an individual by:                a) forming a dispersion by mixing i) a solution comprising a soluble alginate with an insoluble alginate/gelling ion particles or ii) immediately soluble alginate, insoluble alginate/gelling ion particles and a solvent, and        b) dispensing the dispersion whereby the dispersion forms an alginate gel matrix.        
The present invention aims to provide a sterile, ready-to-use alginate-based aqueous composition of neutral pH that has excellent storage stability, that can be directly applied as such at the site of trauma, and that is easy to manufacture. In particular, the present invention relates to a sterile alginate-based aqueous gel formulation that can be produced using heat sterilization of the total composition and that is heat stable as well as storage stable in terms of pH and rheological properties (e.g. viscosity).